Approach for A Successful Legacy
Always present, rarely seen, and increasingly essential, the fast-growing area of Chemistry, Manufacturing and Controls (CMC) of pharmaceutical products is slowly emerging as a titan in its own right.
Music fans may have no idea who Sir Richard Starkey is, but they're sure to know Ringo Starr. The longtime Beatle wasn't the first drummer to play with the band, nor was he the top-billed act on the band's records. Yet without Ringo, The Beatles never would have become The Beatles.
Today that seems self-evident. But in 1960 and '61, Pete Best was playing with Paul, John, and George while Ringo was still with Rory Storm and the Hurricanes and making a name for himself as a drummer. But then in August 1962, The Beatles dismissed Best and added Starr, and his rise to fame began. CMC’s rise to titan status in drug development is following a similar track.
CMC Regulatory Affairs (CMC RA) plays a pivotal role in the development, licensure, manufacturing, and ongoing marketing of pharmaceutical products. In this role, CMC RA professionals help ensure that pharmaceutical products are consistently effective, safe and high of high quality for consumers.
Our growing scientific knowledge and technical experiences have given rise to complex biopharmaceutical manufacturing processes and products. This increase in complexity has led to an ever-growing and evolving set of regulatory agency expectations regarding CMC activities. It is most critical that sponsor companies understand what defines regulatory compliance for their type of pharmaceutical product and the resources behind it.
Finding a Rhythm
To conduct clinical studies and market pharmaceutical products, sponsors are legally required to obtain and maintain regulatory approvals. Regulatory Affairs (RA) is a discipline and strategic function within the overall organizational structure of a pharmaceutical company that directly interacts with government regulatory agencies concerning regulatory approvals.
CMC RA is the body of information that defines not only the manufacturing process itself but also the quality control release testing, specifications and stability of the product together with the manufacturing facility and all of its support utilities, including their design, qualification, operation and maintenance.
CMC regulatory compliance is seen as a process of governance which ensures CMC practices are carried out in agreement with regulatory agencies requirements and expectations. Since such requirements and expectations change with time, a function of CMC regulatory compliance is to ensure that all CMC practices are updated accordingly.
In 2004, the US Food and Drug Administration (FDA) launched the Critical Path Initiative, a project that was intended to improve the drug development processes, the quality of evidence generated during development, and the outcomes of clinical use of these products.
FDA’s mission is to protect and promote the health of the public. With respect to drugs, and biological products, this translates into ensuring reasonable product safety while also facilitating the translation of scientific innovations into commercial products.
The ongoing tension between these two objectives results in assertions that FDA requirements are stifling innovation, and simultaneously that FDA standards are too low. The thesis of the Critical Path Initiative is that scientific advances in the development process are the best way to resolve these conflicts to the satisfaction of most parties and to the benefit of the public.
Just as The Beatles decided Best wasn't a fit, perhaps surprisingly, the manufacturing of pharmaceuticals suffers from the problems of drug development in general. Many drug manufacturing processes are characterized by inefficiency, waste, and neglect of modern process control technologies.
Thus, the pharmaceutical manufacturing sector would also benefit from incorporation of new science, technology and extra set of experienced hands.
Getting by, with a little help from friends
This sort of tale isn't unusual in the pharma industry or in entertainment. As an unabashed fan of heartwarming stories, I love reading about an underdog who adapts to win. Starr, interestingly, had to do just that to stay part of The Beatles and win fans who'd become accustomed to Best's back beats. His unique take, derived in part by learning to play a right-handed drum kit despite being naturally left-handed, ultimately won fans over and led to a decades-long solo career that's still going. It's Ringo on his own terms.
Today accelerated clinical development programs will usually also decrease the amount of time available for the development and understanding of the drug substance, the drug product and their associated processes; therefore, there must be a strategy to ensure that the critical aspects of CMC provide assurance that safety and quality will not be compromised.
This strategy must also assure the flexibility needed to deliver consistent and reliable supplies of product to patients in a less predictable environment, with potential controlled distribution to patients.
DSI, for its part, became so good at CMC regulatory, technical, and project management consulting services to drug sponsors that manufacture and/or market pharmaceuticals, biopharmaceuticals, and cellular and gene therapy products.
Since 2007 we have provided our clients with innovative strategies and exceptional quality work products intended to enhance product development, approval, and marketing presence.
Whether advocating CMC strategy, directing CMC operations or developing CMC submission content that represent the best interests of emerging biotech sponsors, we focus on the critical CMC issues and build programs that enhance development.
It’s very common for pharmaceutical companies to utilize CMC Regulatory Affairs consultants. CMC RA consultants can provide the knowledge, experience, guidance, and advice to help most effectively and efficiently achieve the highest probability of success in obtaining regulatory approval of a pharmaceutical product.
The CMC story is every bit as turbulent and delightful as Starr's. (Seriously, if you haven't sampled some of Ringo's solo work, you should. It's worth it.)
Of course, this is nothing but a thought exercise. The point in doing it is that, in my experience, exceptional strategies are never, ever found in the guidelines. Studying history and the repeating patterns that reveal how outliers become outliers is far more useful. For both DSI and Starr, pleasing customers with a unique style and offering has made them what they are — and impossible to replace.
Whether you're talking drug development or entertainment, that's a good position to be in. What are the most significant CMC issues your company faces and how can these be resolved? It's on our playlist.